Tiragolumab

1整体表现虎落平阳的肿瘤一哥罗氏，医药板块的业绩在去年上半年一波起色后，又陷于环比停滞，因而市值也就只能在$250b左右徘徊不前。全年指引基本维持不变，收入增长预计在mid single digit、EPS增长也就high single digit，这就很欧洲。2已上市产品过去两年独撑业绩危局的眼科双抗Vabysmo渐有触顶之态，好在Phesgo勉强顶上来，但整个产品梯队中已然看不到大额增量的来源，不过好在LOE的一堆抗体药物已经出清得差不多了，因此整体看起来还能保持同比微涨的趋势。肿瘤板块在彻底挥别老一代传奇重磅品种之后，新生代虽有表现，但仍难达到续写辉煌的水平。HER2复方抗体Phesgo的市场转化率已经爬升到47%，距离公司宣称的50%目标已所剩无几，单季接近CHF600m，应该有在中国通过谈判纳入医保目录的贡献，LTM累计CHF1.9b；ADC药物Polivy在1L DLBCL的份额也爬升至31%，单季CHF358m、LTM累计CHF1.2b；而两款CD20/CD3双抗在末线依然无甚起色，单季合计迟迟无法突破CHF100m，即使距离公司宣称的末线峰值销售额CHF700m也遥遥无期。自免板块最核心的仍是Ocrelizumab，皮下制剂看起来正在兑现预期，持续推动销售额爬坡，单季CHF1.8b、LTM累计CHF6.9b，而且4月已拿到J-code，此外皮下制剂有50%新患此前并没有用过Ocrelizumab，这都验证着皮下制剂确有可能大幅延长Ocrelizumab的生命周期。公司维持着峰值销售额CHF8.5b的预期，其中皮下制剂占CHF2b。前两年事实上ROG业绩的扛把子，终于也开始放缓：眼科双抗Faricimab环比下滑，单季CHF1.2b、LTM累计CHF4.0b，主要是美国市场新患的市场份额已经高达60%、以及基金会赠药的减少，只能靠欧洲和刚进医保的中国市场，公司预计年内还能维持20%左右同比增长；而血友病双抗Emicizumab因美国渠道商采购节奏的影响出现环比回落，欧洲也基本失去增速，只有国际市场还有70%同比增速；SMA药物Risdiplam连续多个季度走平，基因治疗Elevidys获批后短暂单季破CHF100m后又迅速滑落。3在研管线就凭现在这个核心管线进展图，已经有点难以想象ROG曾经是肿瘤霸主，而今的研发重点则迁移到心血管代谢、神经、自免等方向，甚至季报里公然出现了“Roche's commitment to become a leader in CVRM”这种违背祖宗遗训之词。既然都CVRM leader了，任何减肥靶点都不能错过，于是这个季度就以$1.65b upfront + $3.6b milestone拿下了Zealand的Amylin类似物Petrelintide，这是继Carmot之后在减肥领域FoMo心态的又一次淋漓尽致的体现。接下来是神经板块的两个重要管线数据读出：TfR1介导的透脑抗体Trontinemab，公布了1/2期临床中期分析数据，给药28周后1.8和3.6mpk剂量组的Aβ PET转阴比例为65%和81%，并且ARIA发生率较低；α-synuclein单抗Prasinezumab公布了2b期临床PADOVA试验的左旋多巴胺治疗人群的结果，虽然整个试验主要终点未达到显著性，但这个subgroup勉强显著，HR=0.79（0.63, 0.99）、p=0.0431，维持着这个靶点继续走下去的希望。然后是自免板块，在TCE和CAR-T风起云涌的背景下，朴实无华的CD20单抗Obinutuzumab在NEJM上发表了三期临床REGENCY试验结果，给药76周后，Obinutuzumab联合SOC（霉酚酸酯+糖皮质激素）与单纯SOC对比，肾脏缓解率CRR为46.4% vs 33.1%，p=0.0232，sBLA已提交，PDUFA在今年10月；不过另一边Ocrelizumab高剂量组却在治疗RMS的三期临床MUSETTE试验中未能达到主要临床终点。此外还有一个重要管线，二代血友病双抗NXT007进入三期临床（一代Hemlibra年销售额高达CHF4.6b），在NVO的Mim8三期临床已经读出的背景下，ROG也势必要维护在这一细分适应症的地位。那么肿瘤板块呢？主要就看TIGIT单抗Tiragolumab从失败走向失败，联用PD1治疗nsq-NSCLC的SKYSCRAPER-06因未能显著改善OS而被正式终止，联用PD1治疗食管癌的SKYSCRAPER-07也被终止，连同过去几个季度的各种坏消息，TIGIT目前也只剩HCC等少数几个瘤种明面上还在开发……除此以外，值得关注的进展还包括：Susvimo获得FDA批准治疗DME，Glofitamab联用GemOx获得欧洲批准治疗2L+ DLBCL，Mosunetuzumab联用Polivy治疗2L+ DLBCL的三期临床SUNMO试验积极结果公布等。Roche总给人一种值得进商学院教科书的感觉，其兴也肿瘤、其落也肿瘤，最强大的能力铸就了曾经的辉煌、也可能恰恰成为眼下的桎梏。如今的Roche，从巅峰落下后短短几年时间，无论是业绩支柱、还是重点研发方向，几乎已经看不到多少当年在肿瘤领域叱咤风云的影子，不知道在心血管代谢、神经、免疫等领域的救赎，是否还能复现Genentech时代的威仪？罗氏ROG往期季报分析：【医苑观畴】主流技术方向谁说了算：2022年上半年全球大药企核心产品管线进展总览【医苑观畴】主流技术方向谁说了算：2022年下半年全球大药企核心产品管线进展总览【医苑观畴】2023年上半年全球大药企核心进展总览【医苑观畴】2024年二季度海外药企进展更新：罗氏ROG【医苑观畴】2024年三季度海外药企进展更新：罗氏ROG

iStock, LevKPhoto Presentations at this year’s American Association for Cancer Research meeting could have a broad impact on the treatment landscape for head and neck and lung cancer, and implications for specific drug modalities like TIGIT and VEGF. On Friday, the streets of Chicago, Illinois—or at least, the halls of its McCormick Place Convention Center—will flood with hundreds of cancer experts from across the country. The annual meeting of the American Association for Cancer Research is in town and will host some of the most cutting-edge research in oncology. Expectations are great for this year’s event, which will host a few highly impactful readouts, some of which could have far-reaching implications for the market and for clinical practice. One of the most anticipated presentations is a detailed readout for Merck’s Phase III KEYNOTE-689 study , which evaluated its blockbuster PD-1 blocker Keytruda in head and neck squamous cell carcinoma (HNSCC). In October 2024, the pharma provided a topline peek at the study’s results, noting that Keytruda elicited a “statistically significant and clinically meaningful improvement” in event-free survival and a “trend toward improvement” in overall survival. Merck did not provide specific data at the time, and Keytruda’s magnitude of efficacy in this indication remains unknown. However, in an April 16 note to investors, William Blair analysts said they expect KEYNOTE-689 to have “read-through to the broader” HNSCC treatment space. “Merck’s Keynote-689 will have some impact on the head and neck cancer landscape/market opportunity,” William Blair analyst Matt Phipps added in an email to BioSpace . Detailed findings from the trial will likely affect other players in this space, including Merus and its bispecific antibody petosemtamab, and Exelixis, which is advancing its oral tyrosine kinase inhibitor zanzalintinib, according to Phipps. Aside from HNSCC, AACR 2025 could also witness big readouts in lung cancer. In an email to BioSpace , AACR president-elect Lillian Siu, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto, pointed to Boehringer Ingelheim’s Beamion LUNG-1 trial, which she said could be “practice-changing.” The trial is studying the HER2 tyrosine kinase blocker zongertinib in non-small cell lung cancer (NSCLC). A Phase Ib readout in September 2024 demonstrated a 66.7% objective response rate for zongertinib, which also shrank tumors in 94% of treated patients. Boehringer Ingelheim is scheduled to release additional findings from Beamion LUNG-1 on Monday . Modality Movement Beyond specific indications, many experts also expect this year’s AACR cycle to be critical for certain treatment modalities. “VEGF-PD(L)1 bispecifics took the oncology world by storm” in September last year, when Summit Therapeutics and Akeso announced that their investigational bispecific antibody ivonescimab bested Keytruda as a frontline NSCLC treatment, Christiana Bardon, co-managing partner at biotech investment firm MPM BioImpact, told BioSpace in an email. The oncology partners doubled down on those results on Wednesday, reporting that the candidate yielded better progression-free survival than BeiGene’s PD-1 inhibitor Tevimbra in patients with NSCLC. “Since [September 2024], a wave of VEGF bispecifics and some trispecifics have emerged,” according to Bardon, who noted that at least 13 of these, including ivonescimab and a candidate developed by Hangzhou DAC Biotechnology and dubbed DXA023-G017 , will have data at AACR. “There’s even a VEGF bispecific with an [antibody-drug conjugate] payload,” she said. Bardon is quick to caution, however, that assets playing in this space “are still mostly at the preclinical stage.” Nevertheless, “they have the potential to disrupt the oncology landscape if successful.” William Blair’s Phipps, for his part, is focused on the TIGIT space, which in recent months has been battered by setbacks. Last month, for instance, BeiGene was forced to scrap its TIGIT asset ociperlimab after disappointing late-stage data, which showed that the candidate was “unlikely to meet the primary endpoint of overall survival” in the Phase III AdvanTIG-302 trial in NSCLC. However, arguably the most high-pro belongs to Roche, which in November 2024 reported that its anti-TIGIT antibody tiragolumab failed the SKYSCRAPER-01 study in locally advanced unresectable or metastatic NSCLC, unable to significantly improve overall survival versus placebo. The pharma did not provide specific data at the time, but will do so at AACR. A more comprehensive readout “will have important implications for the TIGIT inhibitor space,” Phipps said. “We know the trial failed, but are there reasons that can be gleaned that might allow others to still succeed with this target?” Among these other players are partners Gilead and Arcus, which in November 2024 reported Phase III data showing that their anti-TIGIT antibody domvanalimab, when combined with the PD-1 therapy zimberelimab, significantly boosted progression-free and overall survival in patients with a specific type of NSCLC, as compared with zimberelimab or chemotherapy. The partners are also trialing the domvanalimab-zimberelimab combo in HSNCC, for which they are scheduled to present mid-stage data at AACR.